tbuckley/cabot-search huggingface dataset:
Correction: Frequent HLA-DR loss on hematopoietic stem progenitor cells in patients with cyclosporine-dependent aplastic anemia carrying HLA-DR15
Authors: Noriaki Tsuji, Kohei Hosokawa, Ryota Urushihara, Mikoto Tanabe, Yoshitaka Zaimoku, Takamasa Katagiri, Tatsuhiko Ozawa, Hiroyuki Takamatsu, Ken Ishiyama, Hirohito Yamazaki, Hiroyuki Kishi, Seishi Ogawa, Shinji Nakao
Journal: Leukemia (2023)
Doctor who was sexually assaulted at work wins case against trust after it asked colleagues if she had “inappropriate relationships”
Authors: Madlen Davies
Journal: BMJ (2023)

A surgical trainee who was sexually assaulted by a colleague has won an employment tribunal case against her trust after the investigation into the incident questioned her relationships and failed to fully suspend the perpetrator until police told the hospital that he had been arrested for an alleged sexual assault on a girl under the age of 16.
Augmentation Therapy for Severe Alpha-1 Antitrypsin Deficiency Improves Survival and Is Decoupled from Spirometric Decline—A Multinational Registry Analysis
Authors: Daniel D. Fraughen, Auyon J. Ghosh, Brian D. Hobbs, Georg-Christian Funk, Tobias Meischl, Christian F. Clarenbach, Noriane A. Sievi, Karin Schmid-Scherzer, Oliver J. McElvaney, Mark P. Murphy, Adam D. Roche, Louise Clarke, Matthew Strand, Florian Vafai-Tabrizi, Geraldine Kelly, Cedric Gunaratnam, Tomás P. Carroll, Noel G. McElvaney
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Intravenous plasma-purified alpha-1 antitrypsin (IV-AAT) has been used as therapy for alpha-1 antitrypsin deficiency (AATD) since 1987. Previous trials (RAPID and RAPID-OLE) demonstrated efficacy in preserving CT lung density but no effect on FEV1. This observational study evaluated 615 people with severe AATD from three countries with socialized healthcare (Ireland, Switzerland, and Austria), where access to standard medical care was equal but access to IV-AAT was not. Objectives: To assess the real-world longitudinal effects of IV-AAT. Methods: Pulmonary function and mortality data was utilized to perform longitudinal analyses on registry participants with severe AATD. Measurements and Main Results: IV-AAT confers a survival benefit in severe AATD (p<0·001). We uncovered two distinct AATD phenotypes based on an initial respiratory diagnosis - lung indexes and non-lung indexes. Lung indexes demonstrated a more rapid FEV1 decline between the ages of 20 to 50 and subsequently entered a plateau phase of minimal decline from 50 onwards. Consequentially, IV-AAT had no effect on FEV1 decline except in GOLD stage 2 lung index patients. Conclusions: This real-world study demonstrates a survival advantage from IV-AAT. This improved survival is largely decoupled from FEV1 decline. The observation that severe AATD patients fall into two major phenotypes has implications for clinical trial design where FEV1 is a primary endpoint. Recruits into trials are typically older lung indexes entering the plateau phase and therefore, unlikely to show spirometric benefits. IV-AAT attenuates spirometric decline in lung indexes in GOLD stage 2; a spirometric group commonly outside current IV-AAT commencement recommendations. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
PB2595: HEMOGRAM CHANGES IN COMPLICATIONS AFTER COVID IN PREGNANT WOMEN
Authors: Dilafruz Zaynutdinova
Journal: HemaSphere (2023)

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: The health of pregnant women is one of the most urgent medical and social problems not only in Uzbekistan, but throughout the world. In 2021, the incidence of Covid-19 among pregnant women worldwide was 3,500,000, and the number of deaths was 12,300. Aims: Study of hemogram changes in pregnant women with post covid syndrome Methods: Clinical material for the study was obtained from the data of general blood tests of 26 pregnant women who were treated with post-covid syndrome in the department of pathology of pregnant women of the Multidisciplinary Clinic of the Tashkent Medical Academy in 2021. The age of the patients is 19–39 years, the mean age is 26.59 ± 1.62 years. We studied the amount of hemoglobin in the general blood test, the total number of red blood cells. Results: The number of pregnant patients aged 19 to 25 years - 15 (58%), the number of patients aged 26 to 30 years - 5 (19.23%), the number of pregnant patients aged 31 years and older - 6 (22, 77%) When studying the levels of anemia in patients, the number of patients with mild anemia, ie hemoglobin content> 90g/ l - 4 (15.38%), moderate anemia, ie hemoglobin level 90 - The number of patients up to 71g/ l - 16 (61.34%), the number of patients with severe anemia, ie hemoglobin 70g/ l and less - 6 (23.28%) formed. Number of patients with erythrocyte count up to 3.0 * 1012 g/ l - 9 (34.62%), number of patients with 3.0 - 2.6 * 1012 g/ l - 12 (46, 15%), the number of patients with 2.5 * 1012 g/ l and less - 4 (15.38%) The number of patients with a color index from 0.7 to 0.8 - 17 (65.38%), the number of patients from 0.8 to 0.9 - 9 (34.62%) they. The total number of leukocytes from 9.0 to 15.0 * 109 g/ l - 18 (69.23%), the number of patients from 9.0 to 4 * 109 g/ l - 8 (30.77%). When studying the total number of platelets, the number of patients with 180.0 * 109 g/ l - 15 (57.69%), the number of patients with 180.0-150.0 * 109 g/ l - 8 (30.77%), and patients with less than 100.0 * 109 g/ l were found to have 3 (11.54%). Summary/Conclusion: 1. The number of pregnant women aged 19-25 years is 15. 2. Group II, i.e. 2-three months gestation, was recorded in 46% of patients 3. According to the number of hemoglobin and red blood cells, 61.34% of cases of patients with an average severe level of weakness, that is, with a hemoglobin content of 90 to 71 g/l, were recorded. 4. 69.23% of patients with a total number of white blood cells 9.0-15.0 * 109 g/l were identified. 5. Thrombocytopenia was detected in 42% of patients. Keywords: COVID-19, Pregnancy, Complications, Adhesion
Dapagliflozin in Patients With Heart Failure and Deterioration in Renal Function
Authors: Safia Chatur, Muthiah Vaduganathan, Brian L. Claggett, Finnian R. Mc Causland, Akshay S. Desai, Pardeep S. Jhund, Rudolf A. de Boer, Adrian F. Hernandez, Silvio E. Inzucchi, Mikhail N. Kosiborod, Carolyn S.P. Lam, Felipe A. Martinez, Sanjiv J. Shah, Marc S. Sabatine, Lars Kober, Piotr Ponikowski, Bela Merkely, Magnus Petersson, Anna Maria Langkilde, John J.V. McMurray, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2023)

SGLT-2 inhibitors are guideline-recommended in the management of heart failure(HF). While these therapies can be initiated even in patients with comorbid CKD, some patients may face deterioration in kidney function over time. To examine the safety and efficacy of continuing SGLT-2 inhibitors in HF when eGFR falls below thresholds for initiation. Associations between a deterioration in eGFR below 25 ml/min/1.73m2 , efficacy and safety outcomes, and treatment with dapagliflozin were evaluated in time-updated Cox proportional hazards models in a participant-level pooled analysis of DAPA-HF and DELIVER. Among 11,007 patients, 347 (3.2%) experienced a deterioration in eGFR to <25ml/min/1.73m2 at least once in follow-up. These patients had a higher risk of the primary composite outcome (HR 1.87; 95% CI: 1.48-2.35, p<0.001). The risk of the primary outcome was lower with dapagliflozin compared with placebo both among patients who did (HR 0.53; 95% CI: 0.33-0.83) and did not (HR 0.78; 95% CI: 0.72-0.86) experience deterioration in kidney function below eGFR<25ml/min/1.73m2 (Pinteraction=0.17). The risk of safety outcomes including drug discontinuation were higher among patients with deterioration in eGFR<25ml/min/1.73m2 ; however, rates remained similar between treatment groups including among those who remained on study drug. Patients with deterioration of kidney function below eGFR 25ml/min/1.73m2 had elevated risks of CV outcomes yet appeared to benefit from continuation of dapagliflozin with no excess in safety outcomes between treatment groups. The benefit-to-risk ratio may favor continuation of dapagliflozin treatment in patients with HF experiencing deterioration of kidney function.
PB2559: VARIEGATE PORPHYRIA CONFIRMED BY NGS AND TREATED WITH GIVOSIRAN - CASE PRESENTATION
Authors: Georgeta Daniela Georgescu
Journal: HemaSphere (2023)

Topic: 28. Enzymopathies, membranopathies and other anemias Background: Variegate porphyria (VP) is a type of autosomal dominant hepatic porphyria secondary to deficiencies of one of the enzymes involved in heme biosynthesis: protoporphyrinogen oxidase. Hepatic heme biosynthesis defects lead to accumulation of neurotoxic heme intermediates, ALA and PBG that can present acute neurological manifestations and/or cutaneous photosensitivity. Givosiran is a RNA interference therapeutic that targets ALAS1mRNA in the liver to reduce ALA and PBG. Aims: We present a case of a 41 year-old man diagnosed with VP in July 2022 due to intermitent abdominal pain, skin lesions psoriasis like when exposed to the sun and more than two bloody urine episode. He present elevated urine aminolevulinic acid and porphobilinogen during the atack. The diagnosed was confirmed by DNA extraction, NGS sequencing test that shows heterozygous PPOX mutation (NM 001122764.3) c.1065G:C (p.)glu355ASP)). Methods: The 41 year - old man diagnosed with VP was referred to The Hematology Department in August 2022 for treatment with minimal abdominal pain and skin lesions psoriasis like when exposed to the sun, ECOG 0. The laboratory workup showed normal CBC, normal kidney function, Normal LDH, GGT, Alkaline phosphatase, Low level of serum Sodium, 120 mEQ/L, normal GOT, 13.4 UI/L, with high level of GPT, 41.9 UI/L. The urinary tests showed urinary sodium 110 mEq/L, and elevated urine aminolevulinic acid and porphobilinogen. Serum Homocistein level was normal. He starts treatment with Givosiran in August 2022, by subcutaneous administration of 2,5 mg/Kg per month (189 mg/month sc). Results: The Givosiran treatment was well tolerated, with no side effects. The patient was was evaluated clinically and biologically once 3 months after the start of Givosiran administration. He did not present any episode of porphinic attack since August 2022 and until now (03.01.2023), the level of transaminases was normal and urinary ALA and PBG remained at normal values. Fibromax test was normal and hepatitis virus tests for HBV and HCV were negative. Summary/Conclusion: The Givosiran treament for our VP patient was effective and safe. Keywords: Heme, Small interfering RNA, Molecular cytogenetics, Gene expression profile
Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face
Authors: Cristian Navarrete-Dechent, Natalia Jaimes, Stephen W. Dusza, Konstantinos Liopyris, Michael A. Marchetti, Miguel Cordova, Margaret Oliviero, Miguel A. Villaseca, Melissa Pulitzer, Klaus J. Busam, Anthony M. Rossi, Harold S. Rabinovitz, Kishwer S. Nehal, Alon Scope, Ashfaq A. Marghoob
Journal: Journal of the American Academy of Dermatology (2023)
PB2656: APPLICATION EFFECT OF TWO METHODS TO PREVENT SEVERE BLEEDING AT THE PUNCTURE POINT OF FEMORAL VEIN DIALYSIS TUBE IN PATIENTS WITH HEMATOLOGICAL DISEASES
Authors: Xiaoqin Zhou, Xiaoli Chen, LI Wang, Xiaomao Zheng, Xiaomao Zheng
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: When the femoral vein dialysis tube is placed in hematology patients, blood vessel injury will occur due to the thick catheter or low platelet, and even complications such as hematoma, infection and skin swelling will occur. Therefore, effective hemostasis is a crucial step in postoperative nursing. Absorbent gelatin sponge can stop bleeding locally, and at the same time, it can be given local pressure and cold compress immediately. Elastic bandage has good hemostasis effect by elastically pressing the bleeding site, which is a common hemostasis nursing method. Aims: To explore the application effect of two ways to prevent severe oozing at the puncture point of femoral vein dialysis tube in patients with hematological diseases. Methods: From January 2022 to January 2013, 10 patients with persistent severe oozing were selected from the patients who underwent femoral vein dialysis tube implantation in our hospital, and the oozing time was observed and recorded. The patients were divided into control group and observation group in turn according to the recording order, with 5 cases in each group. The control group used gauze dressing+transparent dressing+external application of ice to stop bleeding, while the observation group used absorbent gelatin sponge+transparent dressing+elastic bandage+external application of ice to stop bleeding. The blood leakage at the puncture point of femoral vein dialysis tube within one day, the times of unplanned change of application were observed, and the bleeding duration and treatment efficiency of the two groups were compared. Results: The number of dressing changes per day (1-2 times), blood leakage at puncture point (about 10ml) and bleeding duration (2-3 days) in the observation group were less than those in the control group (P<0.1), and the effective rate of hemostasis treatment in the observation group was better than that in the control group. Summary/Conclusion: The special nursing care of absorbent gelatin sponge+transparent dressing+elastic bandage+external application of ice cubes can reduce the number of dressing changes for severe bleeding at the puncture point of deep vein catheterization in hemodialysis patients in hematology department, reduce the amount of bleeding, shorten the duration of bleeding and improve the treatment efficiency. Keywords: Hematological malignancy
PB2640: ROTATIONAL THROMBOELASTOMETRY AND CALIBRATED AUTOMATED THROMBOGRAM VALUES IN PEDIATRIC CRANIOSYNOSTOSIS SURGERY
Authors: Saskia Luijnenburg, Andreas Machotta, Elise Huisman, Moniek de Maat, C.Heleen van Ommen
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Conventional surgical treatment for craniosynostosis is associated with massive blood loss and dilutional coagulopathy. Haemostasis is usually monitored by activated partial thromboplastin time (APTT) and prothrombin time (PT), but a better assessment of the coagulation state might be obtained by analysis of fibrin clot formation by rotational thromboelastometry (ROTEM), and thrombin generation. Aims: To investigate the effect of dilutional coagulopathy on various coagulation tests in infants who underwent craniosynostosis repair, and to investigate whether various parameters were predictive of perioperative blood loss or transfusion requirements. Methods: In infants 5-25 months undergoing craniosynostosis repair, blood samples were obtained at various timepoints (T1=preoperatively; T3=during surgery; T4=postoperatively; T5=next day). The following parameters were measured: APTT, PT, fibrinogen, ROTEM (clotting time [CT], clot formation time [CFT], α-angle, maximum clot firmness [MCF]), thrombin generation (lag time, peak height, time to peak, endogenous thrombin potential [ETP]). Results: In 108 patients, total perioperative blood loss was 81 ml/kg and transfused red blood cells (RBC) 29 ml/kg. During surgery, APTT and PT levels prolonged, but remained within normal range; fibrinogen decreased to a minimum of 1.3 g/L. For ROTEM parameters, EXTEM-CT and EXTEM-CFT increased during surgery, and EXTEM-α, EXTEM-MCF and FIBTEM-MCF decreased during surgery. Change in thrombin generation parameters is displayed in figure 1: lag time and time to peak shortened during surgery, peak height and ETP decreased during surgery, but increased after surgery. The following day, not all parameters of ROTEM and thrombin generation had returned to the preoperative values. EXTEM-CFT and EXTEM-α were significantly correlated with calculated intraoperative blood loss and transfused RBC; peak height and ETP with estimated intraoperative blood loss. Postoperatively, PT, fibrinogen, EXTEM-CFT, EXTEM- α, EXTEM-MCF were significantly correlated with postoperative blood loss, and PT, fibrinogen and hemoglobin with postoperative transfused RBC. Summary/Conclusion: In children undergoing craniosynostosis repair, ROTEM and thrombin generation provide more insight in situations of dilutional coagulopathy, and may be of use in goal-directed strategies to reduce perioperative blood loss and transfused RBC. Figure 1: Data of thrombin generation perioperatively. Keywords: Thrombin generation, Fibrinogen, Hemostasis, Surgery
PB2639: CHANGES IN PLATELETS IN CHRONIC LIVER DISEASES
Authors: Nodira Nuriddinova
Journal: HemaSphere (2023)

Topic: 32. Platelet disorders Background: Chronic diffuse liver disease is considered one of the crucial problems of modern medicine and occupies one of the leading positions among gastrointestinal diseases. The incidence of chronic hepatitis and cirrhosis of the liver is growing around the world. Over the past decades, the incidence of cirrhosis of the liver remains steadily high, and in specialized hospitals, patients with chronic diffuse liver diseases account for 30% of the total number of patients. The consequences of morbidity lead to the fact that each patient has a long period of incapacity for work, an increase in the level of disability and death. The main causes of death in cirrhosis of the liver are hepatic coma (40-60%) and bleeding from the upper parts of the gastrointestinal tract (20-40%). Liver cancer, intercurrent infections and hepatorenal syndrome are almost rare. Timely detection of this pathology allows you to significantly increase the life expectancy of such patients and improve the quality of life. Aims: determination of platelet changes in the overall blood analysis of patients in chronic liver diseases of viral etiology. Methods: clinical material for the study during 2022, 50 patients with chronic hepatitis C and cirrhosis of the liver, who were treated in the hepatobiliary Department of the multidisciplinary clinic of the Tashkent Medical Academy, received their information from the general blood analysis. The age of patients is 33-76 years, with an average age index of 57.5 years. By the type of disease, patients were divided into 2 groups: group I. 25 patients with chronic hepatitis and group II 25 patients with cirrhosis of the liver. The study examined platelet count data in general blood analysis. Results: When the platelet count in patients was studied, the platelet count was an average of 200 ± 26 x 109 g/l in patients with chronic liver disease, while the total platelet count in patients with cirrhosis of the liver was an average of 96 ± 19 x109 g/l. Patients with cirrhosis of the liver and patients with chronic liver diseases have an increased platelet count in the 3rd month of taking anti-virus therapy. In the 6th month of therapy, the total platelet count decreased in both of them. Summary/Conclusion: In conclusion, we can say that thrombocytopenia develops in liver lesions. If the platelet count approaches the norm after antivirus therapy in chronic hepatitis,it will be possible to see that the patient with cirrhosis of the liver significantly exceeds the results before therapy, even if it is below the norm after therapy. Keywords: Hemostasis, Platelet
P762: HEMATOPOIETIC PROGENITOR CELL-REACTIVE T CELL CLONES CAN RECOGNIZE VIRAL EPITOPES IN APLASTIC ANEMIA BONE MARROW
Authors: Amin Ben Hamza, Carlotta Welters, Monika Brüggemann, Kerstin Dietze, Lars Bullinger, Tim H Brümmendorf, Thomas Winkler, Julian Strobel, Holger Hackstein, Klaus Dornmair, Fabian Beier, Leo Hansmann
Journal: HemaSphere (2023)

Topic: 11. Bone marrow failure syndromes incl. PNH - Biology & Translational Research Background: Aplastic anemia is characterized by bone marrow failure and multi-lineage cytopenia. T cells have been considered key players in immune-mediated aplastic anemia since immunosuppressive therapy with anti-thymocyte-globulin and cyclosporin A is an effective first-line treatment. However, phenotypes and target structures of dominant bone marrow T cell clones are poorly characterized. Aims: We identify immune-phenotypes and target antigens of dominant T cell clones in acquired aplastic anemia bone marrow at the single cell level. Methods: We applied multi-parameter flow cytometry single cell index sorting with subsequent targeted RNA sequencing of T-cell receptor (TCR) αβ and cytokine/transcription factor genes of approx. 8000 T cells from 15 patients with acquired aplastic anemia. Twenty-seven dominant CD8+ T cell clones from eight patients were re-expressed in reporter-T cells to determine reactivity against autologous in vitro expanded hematopoietic progenitor cells and viral epitopes. Results: While none of the 27 re-expressed T cell receptors was activated by CD34- bone marrow, three of them (out of two patients) were activated by magnetically enriched and in vitro expanded CD34+ bone marrow. These progenitor-reactive clones showed a CCR7-CD45RA+CD57+CD28-TBX21+ phenotype, which is indicative of chronic antigen exposure (e.g. viral antigens), and were persistent over time (follow up between five and twenty-four month). Therefore, we tested all 27 TCRs against viral peptide pools and found five of them recognizing epitopes derived from cytomegalovirus (CMV) and one from Epstein-Barr virus (EBV). Interestingly two TCRs recognized both, expanded hematopoietic progenitor cells and viral epitopes. For example, TCR 11A5 was HLA-A*02:01 restricted, recognized expanded progenitor cells, and an epitope derived from the EBV latent membrane protein 1 (LMP1). In vitro testing of an LMP1-minigene did not lead to correct processing/presentation and activation of TCR 11A5 suggesting that additional factors must have contributed to the expansion of T cell clone 11A5 in vivo. Summary/Conclusion: We show for the first time that dominant T cell clones in aplastic anemia bone marrow can be reactive with hematopoietic progenitor cells and epitopes derived from persistent viral infections. Our data suggest a role for chronic viral infections in aplastic anemia pathogenesis as drivers of progenitor cell-directed T cell immune responses. LH and FB contributed equally. Keywords: TCR, Bone marrow failure, Aplastic anemia, Antigen-specific T cells